1. Field of the Invention
This invention relates to the control of disease in animals through the use of oil emulsion adjuvants per se and emulsion priming vaccines containing fatty acid esters, emulsifiers, and surfactants.
2. Description of the Related Art
Vaccines are used for the prevention of disease in animals. The cornerstone of many infectious disease control programs is the induction of specific immunity by vaccination with either live or inactivated microorganisms or their products. Vaccine efficacy depends on many variables, such as the nature and the amount of antigen administered and the presence of adjuvants to enhance immunogenicity. Further, the presence of specific antibody in the serum of young animals, passively acquired from the mother, can seriously impact the effectiveness of the immunization regime.
Water-in-oil vaccines have proven to be more efficacious than vaccines comprised of oil-in-water or aqueous antigen or oil phase alone (Stone, Avian Dis., Volume 27(3), 688-697, 1993). Stone et al. (Av Dis., Volume 34, 979-983, 1990) disclose the use of the terpene oils, squalene and squalane, in a vaccine for Newcastle disease in place of mineral oil. They found that the cumulative HI titers using these oils were similar to mineral oil but the viscosity was up to four times greater than those vaccines using mineral oil. The supply for these terpene oils is limited and more expensive.
Stone (1993, supra) discloses water-in-oil vaccines using animal and vegetable oils. The vaccines contained an aqueous antigen with an oil phase-to-aqueous phase ratio of 4:1. Emulsification was done with both oil-soluble and water-soluble surfactant added to the oil phase. Beeswax was used as an emulsifier for the non-mineral oil vaccines since the known mineral oil surfactants were not suitable for animal and vegetable oil-containing emulsion vaccines. It was reported that the non-mineral oil containing emulsion vaccines had a higher viscosity than mineral oil emulsions of the same relative oil and aqueous components. Low viscosity is an important characteristic for oil emulsion vaccines because it eases the vaccination process, lowering fatigue of working, saving time and work when large numbers of birds are involved. Low viscosity of the oil phase also allows emulsification of a greater amount of aqueous phase for increased volume of antigen or multiple antigens before prohibitive viscosity is reached.
U.S. Pat. No. 5,109,026 to Hoskinson et al., discloses water-in-oil vaccines with mineral oils, squalene, and squalane. The water phase includes a polyanionic polyelectrolyte. Emulsifiers such as ARLACEL A (mannide monooleate) and ARLACEL 80 (sorbitan oleate) were added as oil-soluble emulsifiers with TWEEN 80 (polysorbate 80) as water-soluable emulsifier.
The accepted emulsifying agents for mineral oil vaccines are ARLACEL A (mannide monooleate), ARLACEL 80 (sorbitan oleate), and 80 (polysorbate 80). These easily emulsify water phases in mineral oil but do not function in the same capacity with non-mineral oils. Beeswax is suggested as a surface-active agent for use with non-mineral oil vaccines. However, the beeswax-containing emulsion vaccines have viscosities that are much higher than mineral oil vaccines using emulsifying agents such as ARLACEL A (mannide monooleate) or ARLACEL 80 (polysorbate 80 and TWEEN 80 (polysorbate 80) (Stone, Avian Diseases, Volume 37, 399-405, 1993).
While various water-in-oil vaccines have been developed, there remains a need in the art for oil emulsion formulations to enhance immune responses. The present invention provides oil-emulsion priming vaccines and their non-antigen counterparts. These formulations are different from prior art compositions and their application improves secondary immune responses through increased specific antibody titers and/or avidity and non-specific innate immunity.